This application is a supplement to a recently funded randomized controlled trial, Phytoestrogens in Progression of Atherosclerosis (U01-AT001653). This supplement is focused on the effect of isoflavone-rich soy protein (ISP) supplementation on bone mineral density, bone metabolism and bone turnover in postmenopausal women. Fear and discontent with traditional hormone therapy has resulted in an escalating use of soy products as a postmenopausal therapeutic alternative. However, current information derived from clinical trials of the efficacy of soy on bone health has been limited since studies have been of short duration (mostly 3-12 months) and conducted in small sample sizes. Data concerning the effects of soy on bone health from long-term trials conducted in a large cohort of postmenopausal women are missing. As such, the design, duration and size of the parent trial make it an ideal platform upon which to adequately assess the effects of ISP supplementation on bone health. Since the central portion of the clinical trial has been funded, a very robust database will be obtained at considerable savings. The objective of this supplement is to investigate the effect of ISP supplementation on bone mineral density, metabolism and turnover in 300 healthy postmenopausal women in a 2.5 year, randomized, double-blind, placebo-controlled trial. The 4 Specific Aims are: 1) To determine the effect of ISP supplementation on bone mineral density; 2) To assess the effect of ISP on markers of osteoblast activity by measuring serum bone-specific alkaline phosphatase; 3) To assess the effect of ISP on markers of osteoclast activity by measuring urinary excretion of N-telopeptide; and, 4) To assess the effect of ISP supplementation on regulation of bone turnover by measuring serum RANKL and osteoprotegerin. We hypothesize that ISP supplementation will attenuate bone loss associated with aging and/or postmenopausal estrogen loss. Providing direct evidence for the efficacy of ISP in reducing osteoporosis with a clinical trial using well-validated measurements of bone mineral density, bone metabolism and bone turnover has immense public health implications for women's health. [unreadable] [unreadable]